Williamson is the site of a large rail yard built by the former Norfolk and Western Railroad (now Norfolk Southern Railway), which was built to service the many coal mines of the region. The city is protected by a floodwall, completed by the U.S. Army Corps of Engineers in 1991 in response to devastating floods along the Tug Fork River in 1977 and again in 1984. The wall incorporates floodgates along major access points which, when locked, form a solid barrier against floodwaters. There have only been two uses of the gates thus far: the first occurring in 2002 during a major flood in the region, and the second occurring in 2003, when only two lower lying gates were closed in anticipation of rising water levels.

The local economy is largely fueled by coal mining, transportation, health care and retail.